Diabetes treatment can boost bone health in older women with type 2

Pyridoxamine treatment has potential to prevent fractures and protect bone tissue in postmenopausal women with type 2 diabetes, a study has found.

 

The treatment works by targeting advanced glycation end products and also lowers levels of A1c, an early glycation product.

 

Despite greater bone density and low bone turnover, people with type 2 diabetes have increased fractures risk and higher associated mortality, but previous research linking advanced glycation end products (AGEs) to bone fragility suggests an AGE inhibitor could be a novel therapeutic strategy to prevent the accumulation of AGE in bone tissue.

 

This randomised clinical trial, conducted at the Metabolic Bone Disease Unit of Columbia University Irving Medical Center, New York City, from December 2017 to February 2021, assessed the efficacy of the vitamin B6 metabolite pyridoxamine, an AGE inhibitor, in promoting bone formation in 55 older postmenopausal women with type 2 diabetes.

 

The participants received either 200 mg of oral pyridoxamine dihydrochloride (n = 27; mean age, 75.6 years) or matching placebo tablets (n = 28; mean age, 73.1 years) twice daily for one year.

 

The primary outcome was the change in the levels of the bone formation marker P1NP from baseline to after 12 months of treatment.

 

Other outcomes included changes in bone mineral density measured at the lumbar spine, total hip, femoral neck, and 1/3 radius using dual energy x-ray absorptiometry; A1c levels; and skin autofluorescence at 12 months, a surrogate for bone AGEs. The safety of pyridoxamine was evaluated by monitoring neurologic findings and adverse events because high doses of the parent vitamin B6 have been reported to cause neurotoxicity.

 

At 12 months, pyridoxamine treatment increased P1NP levels by 23% (P = .028) compared with 4.1% with placebo (P = .576), a “nearly significant difference.”

 

Bone mineral density at the femoral neck increased by 2.64% with pyridoxamine but decreased by 0.91% with placebo (P = .007), with no changes at the lumbar spine, total hip, or 1/3 radius. The levels of bone resorption markers or skin autofluorescence were not significantly different between the groups.

 

A1c levels decreased by 0.38% in the pyridoxamine group and correlated with increased P1NP levels, compared with a 0.05% increase in the placebo group (P = .04).

 

Pyridoxamine was well tolerated. Four serious adverse events were reported in the pyridoxamine group and seven in the placebo group; none of these were related to the trial treatment.